MOF-derived cobalt-iron containing nanocomposite with cascade-catalytic activities for multimodal synergistic tumor therapy

Abstract

Reactive oxygen species (ROS)-driven chemodynamic therapy has emerged as a promising anti-tumor strategy. However, the insufficient hydrogen peroxide (H₂O₂) supply in tumor microenvironment results in a low Fenton reaction rate and subsequently poor ROS production and therapeutic efficacy. Herein, we report on a new nanocomposite MIL-53@ZIF-67/S loaded with doxorubicin and glucose oxidase, which is decomposed under the acidic tumor microenvironment to release Fe³⁺, Co³⁺, glucose oxidase, and doxorubicin. The released content leads to synergistic anti-tumor effect through the following manners: 1) doxorubicin is directly used for chemotherapy; 2) Fe³⁺and Co³⁺ result in glutathione depletion and Fenton reaction activation through Fe²⁺ and Co²⁺ generation to achieve chemodynamic therapy; 3) glucose oxidase continuously catalyzes glucose consumption to induce starvation of the cancer cells, and 4) at the same time the produced gluconic acid and H₂O₂ significantly promote Fenton reaction and further boost chemodynamic therapy. This work not only demonstrates the high anti-tumor effect of the new nanocomposite, but also provides an innovative strategy for the development of a multi-in-one nanoplatform for cancer therapy.

Keywords: Chemodynamic therapy; Free radicals; Metal-organic framework; Starvation therapy; Tumor microenvironment.